The long term objective of this research is to further characterize our preliminary finding that vanadium, incorporated into a purified laboratory diet, inhibits some aspect(s) of the post initiation stage(s) of rat mammary carcinogenesis induced by 1-methyl-1-nitrosourea. The specific aims of this work are: 1) to determine the oxidation state, chemical form, and concentration of vanadium in the diet which is well-tolerated and affords the greatest protection against chemically induced mammary carcinogenesis; 2) to characterize the condition(s) required to sustain the protective activity of vanadium against mammary carcinogenesis; 3) to establish the chemical and biochemical form of vanadium which is active against neoplastic development and to clarify the mechanism of transport to and uptake of vanadium by mammary epithelial cells; and 4) to explore various mechanisms by which vanadium may inhibit mammary carcinogenesis. Objectives 1 and 2 will be achieved using the MNU-induced mammary carcinogenesis system. In addressing specific aims 3 and 4 the oxidation state of vanadium and the complexation of vanadium with biomolecules will be characterized by electron paramagnetic resonance and atomic absorption spectroscopies in combination with chemical and biochemical methods. The overall goal of this work is the development of effective methods of breast cancer control and prevention.